This program is designed to further our understanding of renal structure and function in health and disease. Specifically, changes of proximal and distal tubular function and structure will be evaluated in several experimental setting in dogs or rats utilizing renal micropuncture, microperfusion and standard clearance techniques, and light and electron microscopy. In healthy animals, particular emphasis will be directed toward an assessment of the nature and control of sodium and water reabsorption by the renal tubules, the relationship between the intrarenal redistribution of glomerular filtrate and blood flow and changes of renal sodium excretion, molecular transport properties of the isolated perfused tubule, and the influence of various substances on the renal tubular reabsorption of phosphate and glucose. In dogs, particular attention will be directed towards an evaluation of the determinants of responsiveness to various diuretic drugs along the nephron. Furthermore, in rats, clearance and micropuncture studies will be designed to study the pathogenesis and nature of a unique form of massive natriuresis that has been developed in our laboratory. Overall, the results of the program can be expected to further our knowledge of renal function in human conditions associated with alterations of renal function, edema formation, hypertension, the use of diuretic drugs, etc.